Relationship of cyclic stretching of human patellar tendon fibroblasts with abnormal increase of prostaglandins E2 and leukotriene B4 / 中华创伤杂志

ABSTRACT

Objective To investigate the relationship between tendinopathy and higher production of prostaglandins E2 (PGE2) and leukotriene B4 (LTB4) induced by cyclic stretching of human patellar tendon fibroblasts. Methods We used a novel in vitro model system to mimic in vivo conditions, where human patellar tendon fibroblasts (HPTFs) were uniaxially stretched with different magnitudes of stretching (4%, 8% and 12%). Non-stretched fibroblasts were used as control. The productions of PGE2 and LTB4 as well as the expression of cycloxygenase (COX) and 5-lipoxygenase (5-LO) were then measured every four hours of cyclic stretching. In addition, we treated the cells with inhibitors of COX or 5-LO. Results It was found that cyclic stretching of fibroblasts at 8% and 12% of stretching increased PGE2 and LTB4 levels. Blocking the COX enzyme with indomethacin (25 mol/L) decreased PGE2 levels but increased LTB4 production and vice versa. Whereas decreasing LTB4 production with MK-886 (10 ?mol/L) could increase PGE2 levels compared to cells stretched without inhibitors. Conclusions Cyclic stretching of HPTFs produces high levels of PGE2 and LTB4, where a balance exists blocking PGE2 production increases the production of LTB4, and vice versa. Therefore, this study raises the possibility that the routine use of COX inhibitors in clinical treatment of tendinopathy may exacerbate the condition by causing neutrophil-mediated inflammatory and degenerative changes in the tendon due to increased levels of LTB4, which is a potent chemoattractant for neutrophils.